Biosensors usually analyze a sample of a biological fluid, such as whole blood, urine, or saliva. Samples are compositions that may contain an unknown amount of analyte. Typically, a sample is in liquid form and is an aqueous mixture. A sample may be a derivative of a biological sample, such as an extract, a dilution, a filtrate, or a reconstituted precipitate. A biosensor usually determines the concentration of one or more analytes, a substance present in the sample, such as ketones, glucose, uric acid, lactate, cholesterol, or bilirubin. An analysis determines the presence and/or concentration of the analyte in the sample.
The analysis is useful in the diagnosis and treatment of physiological abnormalities. For example, a diabetic individual may use a biosensor to determine the glucose level in blood for adjustments to diet and/or medication. Biosensors may be underfilled when the sample of the biological fluid is not large enough. An underfilled biosensor may provide an inaccurate analysis of the biological fluid. The ability to identify and prevent these inaccurate analyses may increase the accuracy and precision of the concentration values obtained from the biosensor.
Many biosensors measure an electrical signal to determine the analyte concentration in a sample of the biological fluid. The analyte typically undergoes an oxidation/reduction or redox reaction when an excitation signal is applied to the sample. An enzyme or similar species may be added to the sample to enhance the specificity of the redox reaction. The excitation signal usually is an electrical signal, such as a current or potential. The redox reaction generates an output signal in response to the excitation signal. The output signal usually is another electrical signal, such as a current or potential, which may be measured and correlated with the concentration of the analyte in the sample.
Most biosensors have a measuring device and a sensor strip. A sample of the biological fluid is introduced into a sample chamber in the sensor strip. The sensor strip is placed in the measuring device for analysis. The measuring device applies the excitation signal to electrical contacts connected to electrical conductors in the sensor strip, which typically connect with working, counter, and/or other electrodes that extend into the sample chamber. The electrodes convey the excitation into a sample deposited in the sample chamber. The excitation signal causes a redox reaction, which generates the output signal. The measuring device determines the analyte concentration in response to the output signal.
The sensor strip may include reagents that react with the analyte in the sample of biological fluid. The reagents may include an ionizing agent for facilitating the redox of the analyte, as well as mediators or other substances that assist in transferring electrons between the analyte and the electrodes. The ionizing agent may be an analyte specific enzyme, such as glucose oxidase or glucose dehydrogenase, which catalyze the oxidation of glucose in a whole blood sample. The reagents may include a binder that holds the enzyme and mediator together. A binder is a material that provides physical support and containment to the reagents while having chemical compatibility with the reagents.
Many biosensors include an underfill detection system to prevent or screen out analyses associated with sample sizes that are of insufficient volume. Some underfill detection systems have one or more indicator electrodes that may be separate or part of the working, counter, or other electrodes used to determine the concentration of analyte in the sample. Other underfill detection systems have a third or indicator electrode in addition to the counter and working electrodes used to apply an excitation signal to a sample of the biological fluid. Additional underfill detection systems have a sub-element in electrical communication with the counter electrode. Unlike working and counter electrodes, conductive sub-elements, trigger electrodes, and the like are not used to determine the analyte specific signals generated by the biosensor. Thus, they may be bare conductive traces, conductors with non-analyte specific reagents, such as mediators, and the like.
A biosensor uses the indicator electrodes, third electrodes, or sub-element to detect the partial and/or complete filling of a sample chamber within a sensor strip. Typically, an electrical signal passes between the indicator electrode(s), between the third electrode and the counter electrode, or between the sub-element and the working electrode when a sample is present in the sample chamber. The electrical signal indicates whether a sample is present and whether the sample partially or completely fills the sample chamber. A biosensor using an underfill detection system with a third electrode is described in U.S. Pat. No. 5,582,697. A biosensor using an underfill detection system with a sub-element of the counter electrode is described in U.S. Pat. No. 6,531,040.
While these underfill detection systems balance various advantages and disadvantages, none are ideal. These underfill detection systems usually require additional components, such as the indicator or third electrodes. The additional components may increase the manufacturing cost of the sensor strip and may introduce additional inaccuracy and imprecision due to manufacturing variability. These underfill detection systems also may require a larger sample chamber or reservoir to accommodate the indicator or third electrodes. The larger sample chamber may increase the sample size necessary for an accurate and precise analysis of the analyte. Accuracy includes how close the amount of analyte measured by a biosensor corresponds to the actual amount of analyte in the sample. Accuracy may be expressed in terms of the bias of the biosensor's analyte reading in comparison to a reference analyte reading. Precision includes how dose multiple analyte measurements are for the same sample. Precision may be expressed in terms of the spread or variance among multiple measurements.
Additionally, these underfill detection systems may be affected by uneven or slow filling of the sample chamber. The uneven or slow filling may cause these systems to indicate that the sensor strip is underfilled when the sample size is large enough. The uneven or slow filling also may cause these systems to indicate the sensor strip is filled when the sample size is not large enough.
Moreover, these underfill detection systems also may not detect that the sensor strip is underfilled early enough to add more of the biological fluid. The detection may occur after the analysis has started to determine the analytes(s) in the sample. The delay may require replacing the sensor strip with a new sensor strip and a new sample of the biological fluid.
Accordingly, there is an ongoing need for improved biosensors, especially those that may provide increasingly accurate and/or precise detection of underfilled sensor strips and response to underfill conditions. The systems, devices, and methods of the present invention overcome at least one of the disadvantages associated with conventional biosensors.